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Objective: to study the predictive value of the local noninvasive elasticity index of the common carotid artery (CCA) wall in heart transplant recipients. Materials and methods. The study included 101 heart recipients. All study subjects underwent ultrasound examination of carotid arteries with assessment of the damping function of arteries and measurement of local and regional indicators of elastic properties of the CCA. The vascular wall elasticity index (iCOMPL) of the CCA was calculated according to the formula using the CCA diameters in systole and diastole and measurements of systolic and diastolic blood pressure. All-cause death, heart retransplantation, and clinically significant heart transplant coronary artery disease were evaluated as combined endpoints (adverse outcomes).Results. In heart recipients without morphological and immunohistochemical signs of heart graft rejection, detection of relatively low iCOMPL of CCA is a predictor of earlier development of adverse events (p = 0.03). Conclusion. iCOMPL of the CCA is a noninvasive and easily reproducible predictor of adverse out- comes in the long-term period after heart transplantation and can be used in clinical practice for the purpose of risk stratification in heart recipients.

Increased arterial stiffness is an important preclinical indicator of cardiovascular dysfunction, arterial hypertension and target organ injury. This condition increases the risk of long-term adverse events. Solid organ recipients face multiple risk factors for cardiovascular complications due to transplant rejection, lifelong medication use and adaptive features of the transplanted organ. The review presents an analysis of the results of studies on the main functional indicators of peripheral arterial stiffness, as well as the potential effect of immunosuppressive therapy on indicators of vascular stiffness in solid organ recipients.

The emergence of new groups of medications used in the treatment of chronic heart failure (CHF) has made it possible to optimize treatment regimens, changing the clinical status and prognosis in this patient cohort. In this regard, the relevance of individual prognostic markers and risk assessment scales for heart failure (HF) is losing its value. The aim of our review is to summarize the currently available evidence on modern methods of evaluating the functional capabilities of the body and exercise tolerance in CHF patients on the background of systolic dysfunction before heart transplantation.

Background. Cardiovascular diseases are very common among solid organ recipients. They are associated with worsening transplant outcomes. Arterial vascular wall elasticity is an important prognostic indicator and a risk marker for cardiovascular events. Noninvasive measurement of common carotid artery (CCA) elasticity may be useful in assessing cardiovascular risk in solid organ recipients.Objective: To conduct a comparative analysis of indicators of CCA elasticity in solid organ recipients and to study their relationship with factors that potentially have a negative impact on the risk of adverse events.Materials and methods. The study included 154 patients aged 10 to 75 years, including heart (n = 77), liver (n = 9), and kidney (n = 35) recipients, as well as 33 patients with end-stage heart failure waitlisted for heart transplantation (HT). In all participants, carotid artery ultrasound was performed, pulse wave velocity was measured, and CCA elasticity was calculated.Results. CCA elasticity was found to be strongly inversely correlated with age, body mass index, systolic blood pressure, renal tubular filtration rate, CCA intima media thickness, and aortic pulse wave velocity. In heart recipients, CCA elasticity was significantly lower than in liver and kidney recipients (p = 0,002) and it inversely correlated with the length of time elapsed after transplantation, which is probably associated with cardiac denervation.Conclusion. CCA elasticity calculated via noninvasive ultrasound reflects the degree of adverse effects of pathological factors on the main arteries in solid organ recipients.

Heart transplantation (HT) is considered the optimal therapy for end-stage heart failure. In recent years, the number of operations performed has been growing, which has led to a rise in the number of heart transplant recipients requiring outpatient follow-up.Objective: to evaluate the effectiveness of the model of dual personalized follow-up of heart transplant recipients in the consultative and diagnostic department of Shumakov National Medical Research Center of Transplantology and Artificial Organs.Materials and methods. The study included 1,436 patients under outpatient follow-up from January 2008 to December 2022. Recipient data, results of laboratory and instrumental examination methods, nature and frequency of complications at different follow-up periods were analyzed.Results: At the time of discharge from the hospital, 98.7% of patients had received triple-drug immunosuppressive therapy; 6 months later, methylprednisolone was discontinued in 72.2% of recipients. Mean tacrolimus level during the 1-year follow-up was 8.7 ± 2.7 ng/mL; in the period from 1 to 5 years of followup, the mean was 5.1 ± 2.4 ng/mL. At year 1 after transplantation, 23 (1.7%) recipients had been converted to everolimus; by the end of year 5 of follow-up, the number had increased to 8.6%. The most frequently detected complications during outpatient follow-up were: hypertension (48.65%), post-transplant diabetes mellitus (7.24%), nephropathy (35.97%), and malignant neoplasms (4.2%). Recipient survival, excluding in-hospital mortality, was 96.5%; and 88.0% at year 1 and 5 of follow-up, respectively.Conclusion: The dual personalized approach model for outpatient follow-up and treatment of heart transplant recipients will improve recipient survival and quality of life in the long-term post-HT period.

Aim. To establish the prevalence and markers of masked hypertension (HTN) in apparently healthy young people.Material and methods. The cross-sectional study included young people (20-30 years old) with health group I or II, with clinical blood pressure (BP)

The role of frailty in cardiovascular disease is becoming increasingly recognized. Up to 79% of patients with heart failure are frail. Frailty is associated with reduced quality of life and poor prognosis. This review summarizes the available literature on frailty and its key role in waitlisting patients for heart transplantation.

The role of antibody-mediated rejection in predicting survival among heart recipients has been studied in clinical transplantology for over 20 years. This condition is a significant risk factor for heart failure and graft vasculopathy. Antibody-mediated rejection results from activation of the humoral immune system and production of donorspecific antibodies that cause myocardial injury through the complement system. The presence of donor-specific antibodies is associated with lower allograft survival. Treatment of antibody-mediated rejection should take into account the rejection category and the presence or absence of graft dysfunction. The main principle of treatment is to suppress humoral immunity at different levels. World clinical practice has made significant inroads into the study of this issue. However, further research is required to identify and develop optimal treatment regimens for patients with humoral rejection in cardiac transplantation.

Myocardial fibrosis plays a key role in the pathogenesis of heart failure. A family of small non-coding signaling molecules, microRNAs (miRNAs), has been identified as promising profibrogenic biomarkers capable of signaling a possible risk of adverse events after heart transplantation.Objective: to identify and evaluate the diagnostic significance of miRNAs, as well as comprehensive miRNA-based tests in heart recipients with graft myocardial fibrosis.Materials and Methods. The study included 83 heart recipients aged 16 to 64 (48.4 ± 13.1) years. The expression levels of five microRNAs (miR-27, -101, -142, -339, -424) in venous blood plasma were measured by quantitative real-time polymerase chain reaction; galectin-3 serum levels were determined by enzyme immunoassay.Results. Morphological signs of graft myocardial fibrosis were verified in 48 recipients. The miR-27 and miR-339 expression levels were significantly higher in heart recipients with myocardial fibrosis than in those without myocardial fibrosis (p = 0.018 and p = 0.043, respectively). Diagnostically significant threshold levels of miR-27 and miR-339 for detection of myocardial fibrosis in heart transplant recipients were determined (–4.33 and –5.24 units, respectively). The relative risk of detecting graft myocardial fibrosis in recipients with miR-27 expression value above the threshold level was RR = 1.5 ± 0.157 [95% CI 1.104-2.039], p = 0.009; for miR-339, RR = 1.31 ± 0.130 [95% CI 1.018-1.692], p = 0.036. When miR-27 expression levels and galectin-3 serum levels simultaneously exceeded their estimated thresholds, the risk of transplanted heart myocardial fibrosis increased to RR = 2.7 ± 0.456 [95% CI 1.090-6.524], p = 0.032; when miR-339 and galectin-3 simultaneously exceeded threshold values, the risk was RR = 2.0 ± 0.316 [95% CI 1.076-3.717], p = 0.028).Conclusion. The miR-27 and miR-339 expression levels are associated with the presence of fibrotic changes in the graft myocardium. The combination of molecular-genetic and proteomic biomarkers in one test improves the diagnostic characteristics of these expressions with respect to post-transplant complications in heart recipients.

As the survival rate of cardiac recipients improves, higher incidence of malignancy in the late postoperative period becomes essential for their prognosis. Immunosuppressive therapy is one of the key prerequisites for successful transplantation. However, long-term use of immunosuppressive agents increases the incidence of malignant tumors compared to the general population. The risk of their development after organ transplantation increases by 2–4 times compared to the general population. For patients who have undergone transplantation since 2000, the risk of developing malignant neoplasms 1–5 years after surgery is estimated at 10–12%. Timely comprehensive examination of patients, development of new immunosuppression schemes, treatment of those predisposing to the development of malignant neoplasms and giving up harmful habits will reduce the risk of malignant tumors and help diagnose these serious complications at an early stage, which, in turn, will increase the life expectancy of solid organ (particularly the heart) recipients.

Kidney injury in heart transplant recipients is of a complex nature and bears the features of all types of cardiorenal interaction impairment. Pre-transplant renal dysfunction, perioperative acute kidney injury, as well as factors associated with graft and immunosuppression, determine the prevalence and severity of kidney pathology in this group of patients. This review examines the pathophysiology of kidney dysfunction in heart failure, the epidemiology, and criteria for acute kidney injury.

We herein present our initial report from «ROKKOR-recipient», a national multicenter observational study. The prevalence, risk factors, clinical manifestations and outcomes of the novel coronavirus disease 2019 (COVID-19) in solid organ transplant recipients receiving immunosuppressive therapy were investigated. The study enrolled 251 COVID-19 patients (220 kidney recipients, 7 liver recipients, 1 liver-kidney recipient, and 23 heart recipients). The subjects came from 20 regions in Russia. The symptoms, clinical presentation, imaging and lab test results, therapy and outcomes of COVID-19 were described. It was established that solid organ transplant recipients with COVID-19 have a higher risk of developing adverse events. Predictors of adverse events include associated cardiovascular diseases, pulmonary diseases, diabetes, and kidney failure. Symptoms of the disease include dyspnea, rash and catarrhal signs, as well as initial low blood oxygen saturation (SpO2 10 × 109/L), elevated creatinine levels (>130 μmol/L) and a marked decrease in glomerular filtration rate, requiring hemodialysis. Performing organ transplant surgery in COVID-19 does not increase the risk of adverse events but could save the lives of waitlisted terminally ill patients.

Objective: to analyze the correlation between the expression levels of microRNA-101, microRNA-142, microRNA-27, microRNA-339, and microRNA-424 and the plasma concentrations of biomarkers that are potentially significant for the diagnosis of post-transplant complications in heart recipients. Materials and methods. The study enrolled 72 heart recipients, among whom were 56 men (77.8%). The average age of recipients was 48.6 ± 10.9 (16 to 70) years. There were 38 patients with severe chronic heart failure, among whom were 29 men (76.3%). Patients’ mean age was 48.8 ± 9.9 (26 to 70) years. The control group consisted of 12 healthy individuals who did not differ significantly by sex and age. microRNA expression levels in blood plasma were measured via quantitative polymerase chain reaction. Plasma concentrations of VEGF-A, PLGF, MCP-1, and sCD40L were determined using a multiplex method. ST2 and Galectin-3 concentrations were measured via enzyme-linked immunosorbent assay. Results. Patients with end-stage chronic heart failure were found to have significantly higher expression levels of microRNA-27, microRNA-339 and microRNA-424 in blood plasma compared with the healthy individuals. In potential heart recipients, the expression le vels of microRNA-339 and microRNA-424 correlated with serum galectin-3 concentrations, microRNA-101 expression levels correlated with PLGF-1 concentrations, while microRNA-27 expression levels correlated with plasma MCP-1 concentrations. In the early post-transplant period, the expression levels of microRNA-101, microRNA-339, and microRNA-424 in heart recipients were significantly lower than in patients with severe chronic heart failure. In the early post-transplant period (one year or more after transplantation), microRNA-101 and microRNA-27 expression levels were significantly higher than in heart recipients. A year or more after transplantation, the following correlations were found in heart recipients: microRNA-142 expression level correlated with serum levels of galectin-3 (p = 0.05), microRNA-27 and microRNA-424 expression levels correlated with ST2 concentrations (p = 0.02), microRNA-27 expression level correlated with PLGF-1 concentrations (p = 0.02), while microRNA-101 expression level correlated with serum levels of PAPP-A (p = 0.05). Conclusion. In heart recipients, the expression levels of microRNA-142, microRNA-27, microRNA-424, and microRNA-101 correlate with the concentration levels of biomarkers of fibrosis (Galectin-3), rejection (ST2), neoangiogenesis (PLGF), and tissue destruction (PAPP-A). A comprehensive analysis of pre- and post-translational markers may open up new perspectives in diagnosis, assessment of the risks of post-transplant complications, and in understanding the processes leading to their development.

Objective: to determine the diagnostic value of galectin-3 in transplant recipients with myocardial fibrosis and acute heart transplant rejection, verified by endomyocardial biopsy. Materials and methods. The study included 124 patients with end-stage heart failure. Their ages ranged from 16 to 71 (average 48 ± 12) years, of which 106 (85%) were men and 18 (15%) were women. From 2013 to 2016, these patients underwent a heart transplant procedure at the Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation. Analysis of endomyocardial biopsy specimens was used to verify acute cellular, humoral rejection and myocardial fibrosis of the heart transplant. Severity and nature of fibrosis was evaluated using a qualitative imaging technique. Galectin-3 concentration was measured by enzyme immunoassay using Human Galectin-3 Platinum ELISA reagent kits (Bender MedSystems GmbH, Vienna, Austria). Results. In the long-term post-transplantation period, in comparison with the early post-transplantation period, the number of verified graft myocardial fibrosis increased by 88% in recipients who had acute rejection crises and by 37% in recipients who had no rejection crises. Graft myocardial fibrosis was detected more often in recipients who had acute humoral rejection than in those who had acute cell rejection (92% vs 75% of cases, respectively). Plasma galectin-3 levels in recipients with graft myocardial fibrosis was higher than in recipients without it (p = 0.05 1 year and p = 0.01 1–5 years after heart transplantation). In recipients who had acute rejection crises, the risk of developing graft myocardial fibrosis was 1.64 (RR = 1.64 ± 0.1 [95% CI 1.1–2.2]). Conclusion. Galectin-3 is a biomarker for myocardial fibrosis in acute heart transplant rejection.

Objective: to conduct comparative analysis of the expression levels of microRNA-101, microRNA-142, microRNA- 27, microRNA-339 and microRNA-424 in patients with severe chronic heart failure and in heart recipients in the early and long-term period following heart transplantation and to determine the association with acute transplant rejection. Materials and methods. The study included 46 heart recipients, among whom were 36 men (78.3%); the average age of the recipients was 47.7 ± 10.8 (16 to 67) years, and 12 patients with end-stage chronic heart failure, among whom were 8 men (66.7%); the average age of the patients was 46.1 ± 6.4 (37 to 64) years. The control group consisted of 12 healthy individuals, not significantly different by gender and age. microRNA expression levels in blood plasma were determined through quantitative polymerase chain reaction (Q-PCR). Transplant rejection was verified via morphological analysis of endomyocardial biopsy specimens. Results. Blood plasma of patients with end-stage chronic heart failure had significantly higher expression rates of microRNA-101, microRNA-27, microRNA-339 and microRNA-424 than in healthy individuals (p < 0.02). In the early stages following transplantation, the expression levels of microRNA-101 and microRNA-27 in heart recipients were significantly lower than in patients with severe chronic heart failure (p < 0.003). A year or more after transplantation, there were no significant differences in the expression levels of microRNA-101, microRNA- 142, and microRNA-339 in heart recipients and in healthy individuals. In recipients with acute rejection, the expression levels of microRNA-101 and microRNA-27 significantly differed from that of recipients without signs of rejection (p = 0.04 and p = 0.03, respectively). Conclusion. The obtained data on changes in the expression levels of microRNA-101 and microRNA-27 in heart recipients with acute transplant rejection suggests possible diagnostic value of these biomarkers in determining the risk of rejection.

Currently, kidney transplantation and hemodialysis are the primary therapies for end-stage renal disease. High mortality, mostly caused by cardiovascular disease, remains the main challenge in the treatment of this category of patients. It has been shown that in patients with end-stage chronic kidney disease undergoing hemodialysis, the risk of mortality due to cardiovascular disease is up to 20 times higher than in the sex- and age-matched general population. The indicated data determined the appropriateness of isolating cardiorenal relationships into a single cardiorenal syndrome (CRS). Due to the facts mentioned above, intravascular imaging methods, notably optical coherence tomography (OCT), are particularly important in diagnosing coronary artery lesions. This review analyses the data published to date on the features and capabilities of OCT in CRS patients.

The aim is based on the comprehensive examination of pregnant women to determine the risk factors for preterm labor and develop criteria for its prediction.Materials and methods. In a prospective opened study took part 63 patients at 22–34 weeks of gestation. The study was carried out on the basis of PI “Regional Perinatal Center” ZRC, which is the clinical base of the Department of Obstetrics and Gynecology, ZSMU. The average age of pregnant women was 27.1 ± 0.8 (M ± SD) years. Pregnant women were divided into two groups, depending on the gestation period course. Thus, group I included 44 pregnant women who had TPL (threatened preterm labor), and group II – 19 patients with normal course of pregnancy.In the first day, body mass index was determined and laboratory examinations (progesterone, insulin and cortisol level) were performed.Results. According to the ROC analysis, we obtained the following distribution points: the age of pregnant women over 35 years (sensitivity 33.3 %, specificity 96.1 %), the area under the ROC curve of 0.542 (95 % CI 0.411–0.668, P = 0.6953); body mass index (BMI) ≤22.95 kg/m² (sensitivity 66.7 %, specificity 84.3 %), the area under the ROC curve 0.694 (95 % CI 0.566–0.804, P = 0.01); insulin >31.36 μMe/ml (sensitivity 41.7 %, specificity 90.2 %), the area under the ROC curve 0.505 (95 % CI 0.376–0.633, P = 0.96); cortisol ≤609.7 ng/ml (75 % sensitivity, 55 % specificity), the area under the ROC curve of 0.694 (95 % CI 0.518–0.765, P = 0.07); progesterone

Aim: to study plasma galectin-3 levels in heart recipients and to determine the potential significance of galectin-3 level in acute transplant rejection and fibrosis.Methods. The study included 107 heart transplant recipients, aged 16 to 70 (48 ± 13) years, of which 90 (84%) were men. Dilated cardiomyopathy was diagnosed in 57 patients prior to heart transplantation, end-stage ischemic heart disease in 50. Galectin-3 concentrations and placental growth factor (PlGF) were measured using enzyme-linked immunosorbent assay (ELISA); vascular endothelial growth factors (VEGF-D and VEGF-A), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factors (PDGF-BB), and soluble CD40 ligand (sCD40L) were measured using multiplex technology xMAP. Acute graft rejection and myocardial fibrosis were verified through morphological examination of endomyocardial biopsy specimens.Results. Galectin-3 concentrations in patients with congestive heart failure (15.92 [11.80; 23.65] ng/ ml) were significantly higher than in healthy individuals (11.08 [7.71; 14.47] ng/ml), p = 0.00. No correlation was found between galectin-3 levels and sex, age and pre-transplant diagnosis. A month after transplantation, plasma galectin-3 level was significantly higher than before transplantation; a year later, the levels decreased to pre-transplant levels (18.71 [13.14; 25.41] ng/ml). By the end of the first year after transplantation, the levels were significantly higher both in patients with 1-2 episodes and in the patients after 3 or more episodes of acute rejection, in contrast to recipients who were not diagnosed with rejection. By the end of the first year after heart transplantation in patients with fibrosis, plasma galectin-3 levels were significantly higher than in patients without fibrosis. By the end of the first year after heart transplantation, galectin-3 levels in the recipients were associated with the nature of myocardial fibrosis: in patients with diffuse focal fibrosis (22.52 [20.98; 26.08] ng/ml), plasma concentrations of galectin-3 were significantly higher than in patients without fibrosis (15.36 [11.95; 22.42] ng/ ml, p = 0.01).Conclusion. Plasma levels of galectin-3 in heart recipients by the end of the first year after transplantation is associated with previous crises of acute graft rejection, irrespective of the number of rejection episodes. Elevated plasma levels of galectin-3 in heart recipients in the long term after transplantation is associated with myocardial fibrosis; galectin-3 levels are associated with the morphological characteristic of fibrosis in the transplanted heart (diffuse focal fibrosis).

Abstract. Despite improvements in immunosuppressive therapy, antibody-mediated rejection (AMR) remains one of the most important risk factors for poor prognosis for survival of recipients, cardiac graft dysfunction, and cardiac allograft vasculopathy (CAV) after heart transplantation.Aim: to assess the incidence of case of antibodymediated rejection and cardiac allograft vasculopathy depending on the gender of the patients who underwent heart transplantation in our Center from January 2010 to December 2017.Methods. The median observation was 42 months. The study comprised 606 patients (84 [14%] women) who underwent heart transplantation in 2010 to 2017. We analyzed all the episodes of antibody-mediated rejection, which were diagnosed by the results of endomyocardial biopsies.Results. We comparing the total incidence of antibody-mediated rejection and we are found significant differences among men and women who underwent heart transplantation (p < 0.05), the survival rate during the first year after heart transplantation was 95 and 92%, respectively. The incidence of antibody-consistent rejection was significantly higher among women who had a history of pregnancy and/or use of mechanical circulatory support systems (UNOS status 1A) in the pre-transplantation history (p < 0.05), and we also found significant differences in the incidence of cardiac allograft vasculopathy in women diagnosed with AMR (p < 0.05). The survival rate among women within a year after the diagnosis of AMR is 83% compared to 96% of the recipients free from AMR.Conclusions. Women are at higher risk for AMR after heart transplantation and it increases their risk for cardiac allograft vasculopathy. Females recipients may more frequent myocardial control biopsies and a personalized approach in prescribing immunosuppressive therapy. Women-recipients of transplanted heart should undergo These measures will help to identify in time the development of antibodymediated rejection and reduce the incidence of cardiac allograft vasculopathy after heart transplant.

Aim. To estimate the frequency and expressiveness of atherosclerotic lesions of the transplant coronary arteries of the determined by an angiographic method.Materials and methods. Coronary angiography was executed to 518 recipients of heart aged from 10 till 72 years (average 56,92 ± 12,1) within the first week after transplantation of heart (a median 6; 3–42 days). Men – 466, women – 52. Initial status of recipients: UNOS 1A – 217 of people, UNOS 1B – 89 of people, UNOS 2 – 212 people. Included the following criteria of the donor in the analysis: sex, age, cause of brain death.Results. Angiographic signs of atherosclerotic lesions of coronary arteries are discovered in 166 cases, in 65 cases defined as significant stenosis which demanded performance of the percutaneous coronary intervention (PCI). In 352 cases symptoms of atherosclerosis are not revealed (group of comparison). At recipients in the status UNOS 1A and UNOS 1B discovered the transmission of atherosclerosis (TA) more often, than recipients in the status UNOS 2 (54% and 36%, respectively). Age of donors in group with transmission of atherosclerosis was 50,2 ± 0,7 years, and in group of comparison – 41 ± 0,6 years (r = 0,0005). Range of donors age in groups did not differ and made 18–66 years for group of comparison and 20–67 years for group with transmission of atherosclerosis, but in subgroup of PCI made 31–67 years. Gender influence on the frequency of transmission of coronary atherosclerosis it is not revealed. Acute violation of brain blood circulation as the cause of brain death was observed in 76% of cases at TA group and 61% in group of comparison.Conclusion. The age of the donor and acute violation of brain blood circulation are the factors associations with probability of transmission of coronary atherosclerosis, however it is important to consider the status of the recipient.

Heart transplantation is the «gold standard» of treatment severe heart failure. Patient survival after heart transplantation has improved dramatically since the availability of calcineurin inhibitor (CNIs). However, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction and reduces long-term patient survival. Use mTOR inhibitor in immunosuppressive therapy may improve renal function when everolimus is administered associated with a progressive reduction of CNIs. The purpose of our report is to demonstrate the successful case of conversion of the recipient after heart transplantation to everolimus and to evaluate the effectiveness of this drug during the observation year after heart transplantation.

Despite the fact that many national and foreign scientific groups are working to address the issue of preterm labor, the rate of miscarriage ranges from 5.0 to 10.0 % without decreasing trend. The aim: to determine the efficacy of progesterone and thiotriazoline combination in the risk of premature birth on the basis of studying the hormonal profile dynamics and perinatal consequences. Materials and methods. Serum progesterone levels as the main hormone of pregnancy, insulin, cortisol were measured in pregnant women with the threat of preterm labor (TPL) and in the umbilical cord blood; insulin-cortisol index was calculated. Pregnant women were divided into two groups: 1 - basic (n = 22), and 2 – comparison group (n = 22). For hormonal disorders correction and pregnancy prolongation patients of basic group with TPL at 22–34 weeks of gestation received preparations of progesterone and thiatriazoline: natural micronized progesterone vaginal suppositories, 100 mg, twice-daily and0.2 g of thiatriazoline rectal suppositories 1 time per day for 10 days. Comparison group patients at the 22–34 weeks of gestation received standard treatment according to approved clinical protocols. Results: Analysis of the progesterone, cortisol and insulin blood serum baseline levels of both pregnant women study groups showed no significant difference. In the basic group the progesterone level during 10 days of treatment decreased from 162.5 ng / ml to 148.8 ng / ml (P > 0.05). There was no significant difference between the progesterone contents before and after treatment in both groups. In pregnant women the insulin level increased from 15.9 μMe / ml to 34.7 μMe / ml (P < 0.05). In the comparison group the insulin level also increased from 13.9 μMe / ml to 14.4 μMe / ml, but not significantly. The cortisol level in the basic group insignificantly increased from 564.6 ng / ml to 600.5 ng / ml (P > 0.05). In the comparison group the cortisol level before and after treatment did not change significantly – 536.6 ± 321.6 ng / ml and 546.5 ± 334.2 ng / ml, respectively. There was a significant increase in insulin / cortisol index from 0.027 U.M. to 0.066 U.M. (P < 0.05) in the pregnant women of the basic group after 10 days of treatment. The baseline level of insulin / cortisol index in pregnant women of comparison group, as in the basic group, was 0.027 U.M. After a week of standard therapy it significantly increased up to 0.033 U.M. (P < 0.05). There was no significant difference in the progesterone level in the umbilical cord blood of both study groups (1 – 1483 ng / ml, 2 – 1662 ng / ml). Insulin content in the umbilical cord blood in the basic group was the lowest (3.78 μMe / ml) and significantly differed from that of comparison group (4.29 μMe / ml) (P < 0.05). The levels of cortisol in the umbilical cord blood did not differ between women of the basic and comparison groups – 264.5 ng / ml versus 305.2 ng / ml. The insulin-cortisol index in all groups was not significantly different. Conclusions. In women with a risk of preterm birth the decrease in insulin and cortisol levels in the umbilical cord blood indicates the physiological adaptation to stress factors during pregnancy and the therapeutic strategy chosen effectiveness. The use of micronized progesterone in combination with antioxidants increases the stress hormonal index in the basic group by 2.5 times, indicating the proposed treatment regimen effectiveness and preventing premature birth.

Tricuspid valve insuffi ciency is one of the most common variants of valve pathology of transplanted heart. The review is sanctifi ed to the analysis of modern looks to on causes, potentially infl uencing on development of tricuspid valve insuffi ciency of transplanted heart, and also methods sent to declines risk his development.

Aim: to develop an optimal surgical tactic for implantation of “AVK-N” system as a “bridge” to heart transplantation.Materials and methods. 17 patients were included. They were operated in the period from 2012 to October 2017 in Federal State Budgetary Institution «V.I. Shumakov National Medical Research Center of Transplantology and Artifi cial Organs». A tiny implantable system «Portable device for assisting cardiac circulation» (AVK-N; Russia) was used for replacing the pumping function of the left ventricle. All patients were examined according to the program of potential recipients for heart transplantation, before the applying of prolonged mechanical circulatory support. Among the operated patients there were 16 (94.1%) men and 1 (5.9%) woman, the average age was 52.64 ± 10.56 (from 33 to 67 years). All patients had congestive heart failure III–IV functional class according to NYHA, refractory to optimal drug therapy. Heart failure was triggered by dilated cardiomyopathy in 12 (70,58%) cases, and by postinfarction systolic dysfunction of the left ventricle in 5 (29,42%). Implantation of «AVK-N» system was performed to potential recipients of the donor heart with terminal stage of CHF with a decrease in LV ejection fraction up to 10%.Results. As a result of this study there were developed several technological aspects facilitating the subsequent heart transplantation.Conclusion. Our experience in optimizing the surgical tactics of the “AVK-N” system implantation as a bridge to heart transplantation, demonstrated the possibility and safety of its active use in both patients with terminal heart failure on the waiting list of heart transplantation and patients having temporary contraindications to HTX.

Aim. The study was aimed to assess the prevalence and risk factors of hypertension in cardiac recipients.Materials and methods. End-stage heart failure patients who received cardiac transplant between 01.01.2013 and 31.12.2016 in V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Moscow) and survived 3 months after surgery were included and followed up for 999.4 ± 774.3 (108–1587) days. Young patients (

Hypertension is a common syndrome in adult and pediatric cardiac transplant recipients affecting the great majority of patients. Elevated blood pressure is a major potentially modifiable risk factor associated with cardiac graft failure, vasculopathy, arrhythmias, stroke, renal failure and premature death. This review discusses the magnitude of the problem, its distinct mechanisms, and certain issues of prevention and treatment of post-transplant hypertension.

Aim. To examine the assumption that significant concentrations of cystatin C in urine are the manifestation of the tubular necrosis and, respectively, the severity of kidney damage after heart transplantation (HTx).Materials and methods. In this study we evaluated 33 heart recipients (6 women and 27 men, aged from 24 to 68 years old) who had risk factors of acute kidney injury: serum creatinine level >113 μmol/l and/or mechanical circulatory support requirement (20 patients, in 14 cases before HTx). Cystatin C concentration in serum and in urine was measured by DyaSis particle-enhanced immunoturbidimetric assay test «Cystatin C FS».Results. Recipients were divided into two groups according to the levels of cystatinuria. In the group with the significant (more than 0.18 mg/l) urinary cystatin C concentrations the requirement of renal replacement therapy (RRT) was 2.5-fold higher, and the mean duration of RRT was more than 10-fold longer. In 2 patients with the significant cystatinuria acute kidney injury (AKI) has transformed into end-stage renal disease (ESRD).Conclusion. Due to data obtained we may suppose that significant concentrations of cystatin C in urine are the marker of the tubular necrosis with the prolonged RRT requirement. Further studies are needed to justify this relationship.

Introduction. Venoarterial extracorporeal membrane oxygenation (VA ECMO) is one of the most widely used methods of temporary mechanical circulatory support (MCS) during the preparation and performance of heart transplant surgery (HT) [Barth E. et al., 2012; Kittleson M.M. et al., 2011].Aim of this study was to assess the effectiveness of using peripheral VA ECMO as a method of mechanical circulatory support in potential heart transplant recipients that urgently required transplantation.Materials and methods. The study included 125 potential heart transplant recipients (107 (86%) men and 18 (14%) women) aged from 12 to 72 (43 ± 1.2) years with a peripheral VA ECMO system installed within the period from April 01, 2011 till August 12, 2016. The indication for the start of its use was rapidly progressing congestive heart failure (CHF) of level 1 or 2 by the INTERMACS scale. Femoral blood vessel cannulation was performed using both open (surgical) and closed (puncture) methods. 23 and 25 F venous cannulae were utilized for femoral vein cannulation, and 15 and 17 F arterial cannulae were utilized for femoral artery cannulation. In all cases superfi cial femoral artery catheterization (14 F single-lumen catheter) or cannulation (8 or 10 F arterial cannula) was performed in the descending (anterograde) direction for the prevention of lower limb ischemia on the side of the femoral artery cannulation.Results. The peripheral cannulation method was used to perform VA ECMO in 100% (n = 125) observations. In 69 (55.2%) patients the severity of progressive CHF corresponded to INTERMACS level 1; in 51 (40.8%) cases it corresponded to INTERMACS level 2. During VA ECMO the average volumetric extracorporeal circulation fl ow rate ranged from 2.2 to 4.5 (3.2 ± 0.4 l/min) or 1.6 ± 0.2 l/min/m2 with the average rotation speed of the centrifugal pump of 3.216 ± 105 rpm. 113 (90.4%) of 125 potential recipients underwent HT. The duration of VA ECMO prior to HT (n = 113) was from 8 hours to 40 (7.1 ± 2.7) days: in 37 (32.7%) of 113 patients – up to 3 days, in 43 (38.1%) cases – from 4 to 7 days, in 21 (18.6%) cases – from 8 to 14 days, in 8 (7.1%) cases from 15 to 21 days, in 4 (3.5%) cases – more than 3 weeks. In the course of VA ECMO, 12 (9.6%) of 125 potential recipients (11 men and 1 women aged from 21 to 63 (40 ± 4) died before they could receive HT. In 2 (16.7%) of 12 cases the cause of death was brain death associated with a thromboembolic cerebrovascular event. The majority of patients (n = 10; 83.3%) died of progressive multiple organ failure and sepsis. 6 of 12 patients showed clinical and instrumental signs of acute unilateral (n = 2) or bilateral (n = 4) polysegmental pneumonia.Conclusion. Peripheral VA ECMO provides a successful bridge to heart transplant procedure in 90% of potential recipients who need pre-transplant MCS. The timely initiation of VA ECMO before the development of pronounced hemodynamic, organ, electrolyte and metabolic disorders creates the conditions for a successful use of MCS in potential heart transplant recipients.

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.Materials and methods. The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.Results. No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2.

In this article, the review of the literature on various aspects of the noncompaction cardiomyopathy is presented. Non-compaction cardiomyopathy is a relatively rare congenital heart disease characterized by an excessive prominence of trabecular meshwork, and deep recesses of the ventricular myocardium. The most frequent is left ventricular noncompaction (LVNC). LVNC can occur in isolation or coexist with other cardiac and systemic anomalies. Noncompaction can be detected with an echocardiography or cardiac magnetic resonance imaging. The clinical presentation varies ranging from asymptomatic patients to patients who develop ventricular arrhythmias, heart failure, thromboembolism.

Introduction. Increase in the number of older patients with terminal CHF results in increase in their proportion among potential recipients requiring mechanical circulatory support and/or heart transplantation (HT) [Abecassis M., Bridges N.D. et al., 2012].Aim. To analyze our own experience of HT in recipients of older 60 years.Materials and methods. The study included 63 patients (56 men (93.3% ) and 4 (6.7%) women) aged 60–74 years (63.0 ± 0.8) with body weight of 76.6 ± 1.4 kg, body surface area of 1.7 ± 0.02 m2, and body mass index of 23.4 ± 0.6. Indications for heart transplantation: dilated cardiomyopathy – 24 (38.1%), coronary heart disease – 34 (54.0%), hypertrophic cardiomyopathy – 2 (3.2%), irreversible cardiac graft dysfunction – 3 (4.7%). 46 (73.0%) patients had NYHA functional Class III and 17 (23.0%) patients – Class IV. Transpulmonary pressure gradient was 11.2 ± 2.7 mmHg, pulmonary vascular resistance – 3.5 ± 1.3 Wood units. According to UNOS algorithm 10 (15.9%) patients were listed as Status 1A of urgency of orthotopic cardiac transplantation (VA ECMO, n = 8, and implantable left ventricular assist device, n = 2), 21 (33.3%) patients as Status 1B, and 32 (50.8%) patients as Status 2. Recipients had the following comorbidities: arterial hypertension (n = 51; 81.0%), diabetes mellitus (n = 6; 9.5%), cerebrovascular disease (n = 13; 20.6%), history of stroke (n = 9; 14.3%), dialysisindependent renal dysfunction (n = 21; 33.3%). Before cardiac transplantation 9 (14.2%) recipients underwent various thoracic surgeries, 2 (3.2%) recipients – brain surgery. Heart donors (49 (77.8%) men and 14 (22.2%) women) were aged 18–59 (34.3 ± 10.4) years.Results. ICU hospitalization lasted for 4–15 (8.2 ± 0.5) days. In 61.9% of cases (n = 39) early postoperative and hospital periods were uncomplicated. Early on-table postoperative activation («early» tracheal extubation) was performed in 32 (50.8%) patients in 48 ± 6 minutes after surgery completion. 2 (3.2%) recipients demonstrated early graft dysfunction and required VA ECMO. Complications other than graft dysfunction were in 24 (38.1%) recipients: renal dysfunction (n = 8; 12.7%), renal and hepatic dysfunction (n = 4; 6.3%), infections (bacterial pneumonia, n = 3, [4.8%]), dyscirculatory encephalopathy (n = 9; 14.3%). 12 (19.0%) patients required continuous renal replacement therapy, 10 of them (15.9%) demonstrated renal function recovery. In 2 (3.2%) cases long-term hemodialysis was used. Hospital lethality (n = 6; 9.5%) was due to multiple organ failure syndrome and sepsis.Conclusion. Our own experience demonstrates satisfactory short-term and long-term survival after heart transplantation in recipients of 60 years and older.

In the review a comparative analysis of the treatment of end-stage chronic heart failure using heart transplantation and durable mechanical circulatory is conducted. It shows the main advantages and limitations of heart transplantation and the prospects of application of durable mechanical circulatory support technology. The main directions of this technology, including two-stage heart transplant (bridge to transplant – BTT), assisted circulation for myocardial recovery (bridge to recovery – BTR) and implantation of an auxiliary pump on a regular basis (destination therapy, DT).

Peculiarities of the mode of action and clinical use of fixed low-dose combination of lisinopril and hydrochlorothiazide are discussed. Reasonability of ACE inhibitor and thiazide diuretic combination is supported due to more effective blood pressure control, organoprotection improvement and side events risk reduction. Results of the clinical studies on efficacy and safety of this combination in hypertensive patients with different concomitant diseases are presented.

This review summarizes the current literature devoted to the analysis of prognostic role of ST2 biomarker in rejection of the transplanted heart. ST2 is one of the most promising diagnostic markers of the development and severity of heart failure as well as the mortality risk in patients with cardiovascular diseases. ST2 is expressed in cardiomyocytes in response to a variety of pathological processes and mechanical damage to the heart, which allows diagnosing cardiovascular diseases before clinical manifestations. Presumably, measuring the level of ST2 in heart transplant may have diagnostic and prognostic value in the assessment of graft and risk of rejection. Currently, accumulated clinical data on the role of given biomarker in heart transplantation are not enough, and further research on the relation of ST2 levels with different clinical and laboratory parameters in heart recipients is necessary.

Introduction. The Quilty Effect (lymphoid-cellular infiltration of the endocardium) is a frequent finding in biopsies of the transplanted heart. The role of this phenomenon in the rejection of the transplanted heart remains unclear. Aim. Retrospective analysis of endomyocardial biopsies of the transplanted heart and assessment of the relationship between acute cellular rejection and Quilty Effect. Methods and results. 112 endomyocardial biopsies with Quilty Effect were identified out of 883 studied biopsies during the period from January 2010 to June 2014. The frequency of Quilty damage occurrence in acute cellular rejection is significantly higher than in its absence (17.7% and 5.6%; р < 0.001). The combination of acute cellular rejection with acute antibodymediated rejection significantly increases the frequency of Quilty damage (р = 0.039). Isolated acute antibodymediated rejection of the transplanted heart does not affect the frequency of Quilty Effect occurrence and is not a direct etiologic and pathogenetic factor of this phenomenon. In the absence of acute cellular rejection, Quilty Effect is a predictor of its later development. Mild acute cellular rejection in conjunction with the Quilty Effect causes the risk of more severe degree of rejection. Quilty Effect type B occurs much less frequently than type A (1.9% and 10.8%; р = 0.001) and is observed primarily in acute cellular rejection of grade G2R (р = 0.001); the frequency of these morphological types at various periods after heart transplant was not significantly different (р > 0.05). Conclusion. The Quilty Effect is a kind of manifestation of acute cellular rejection of the transplanted heart when immunosuppressive therapy with calcineurin inhibitors is used.

Aim. Identifi cation of possible histological differences of the Quilty effect in acute rejection and its absence as well as studying the proliferation of blood and lymph vessels in the area of Quilty damage.Materials and methods. 883 endomyocardial biopsy materials from 352 patients were studied. Histological sections were stained with hematoxylin and eosin, Masson method; the endothelium of lymphatic vessels was stained with immunoperoxidase method using a marker D2-40.Results. The Quilty effect was observed both in acute rejection and inits absence. In the majority of cases the Quilty effect was of type «A» and it was combined with acute rejection. The Quilty effect of type «B» has been mostly in the G2R. Acute rejection is characterized by diffuse form of endocardium lymphoid infi ltration. Follicular form resembles lymphoid organ tissue. Different types and forms of the Quilty effect may be combined in the same biopsy. Proliferation of blood vessels presents in the area of the Quilty effect. Lymphatic vessels are missing in endocardium and in the area of the Quilty effect. They could be found only in the myocardium of endomiocardial biopsy.Conclusion. Diffuse lymphoid infi ltration of the endocardium is a characteristic feature of acute rejection of the transplanted heart. Follicular form of the Quilty effect is similar to lymphoid tissue whose role requires further study using immunohistochemical methods.

In cardiac recipients non-invasive monitoring will identify the risk of acute rejection, as well as reduce the number of routine biopsies. The relation between the development of the transplanted heart rejection and the change of elastic properties of common carotid artery has been proved. Aim: to analyze dynamics of iRIG in treatment of graft rejection in heart recipients.Materials and methods. 59 heart recipients were examined: 21 patients (pts)without rejection, 20 pts – with rejection after 1st biopsy, 15 pts – with rejection after 1st and 2 biopsies, 3 pts – with persistent rejection after all biopsies. iRIG was estimated using empirical equation.Results. Dynamics of iRIG in pts. without rejection according to all biopsies over time was not signifi cantly changed 6280 ± 2143, 6083 ± 2388, 6362 ± 1984 and 6188 ± 3012 cm/sec2 (p = 0.11, p = 0.13, p = 0.17 between the 1st and 2nd, 2nd and 3rd, 3rd and 4th values, respectively). In pts. with rejection iRIG decreased during treatment, but was signifi cantly higher even after successful treatment. In patients with persistent rejection iRIG did not decrease and tended to increase (17 459 ± 9702 cm/sec2 on the results of the 1st biopsy to 21 305 ± 10 448 cm/sec2 on the results of the 4th biopsy).Conclusions. In patients with heart transplant iRIG does not change signifi cantly with the time after transplantation. iRIG increases in all types of rejection, followed by its decrease in the course of therapy; in patients with persistent rejection iRIG remains high. Evaluation of iRIG can be used for non-invasive monitoring of patients after heart transplantations (HTx) and to identify patients at high risk of transplant rejection.

Aim: to determine the clinical significance of vascular endothelial growth factors VEGF-A, VEGF-D, PlGF-1 to assess the risk of cardiovascular complications in heart recipients. Materials and methods. 103 patients, aged 16 to 73 years, 85 males and 18 females. 65 recipients (47 men and 18 women) had dilated cardiomyopathy, 38 – coronary heart disease (CHD). The concentration of VEGF-A, VEGF-D, PlGF-1 was measured using xMAP technology with sets of reagents Simplex ProcartaPlex™. Results. After HTx the level of VEGF-A significantly decreased, p = 0.001. There were no correlations between the levels of VEGF-A, VEGF-D and PlGF-1 with age, gender and diagnosis. After HTx VEGF-A level was higher in recipients with ACR than in those without it (p = 0.001). ACR frequency was significantly higher in patients with high VEGF-A level (≥316.5 pg/ml, RR = 5.8 ± 0.5, AUC = 0.779). After HTx PlGF-1 level was higher in recipients with ACR too (p = 0.039). ACR frequency was significantly higher in patients with high PlGF-1 level (≥5.33 pg/ml, RR = 1.8 ± 0.5, AUC = 0.65). There were no correlations between VEGF-D level with ACR and all three biomarkers with AMR. ACR frequency was significantly higher with both high VEGF-A and PlGF-1 levels (RR = 6.4). Conclusion. Serum levels of VEGF-A and PlGF-1 after HTx may be regarded as indicators of increased risk of ACR.

Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW) variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts). Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD) pts without decompensated heart failure were included. Along with resistive index (Ri), pulsative index (Pi), and CCW intima-media thickness (IMT), CCW rigidity index (iRIG) was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7%) and 17 (18.3%) cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001). Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9) sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84.3%. Conclusions. Increased carotid wall stiffness is found in patients with both antibody-mediated and cellular car- diac allograft rejection. Non-invasive measurement of carotid artery wall rigidity index with triplex ultrasound is a simple screening tool for risk stratification. Having a functional marker would enable preventive measures to be taken at the early stages.

Aim of study: multiplex analysis of the levels of biomarkers of neoangiogenesis and inflammation in cardiac transplant recipients. Materials and methods. 59 pts. with heart failure III–IV according to NYHA FC, waiting for a heart transplant, aged 22 to 73 years, 48 males and 11 females. 41 recipient (30 men and 11 women) had dilated cardiomyopathy, 18 – coronary heart disease (CHD). The concentration of VEGF-A, VEGF-D, PlGF, PDGF-BB, FGF, sCD40L, MCP-1 was measured using xMAP technology, the sets of reagents Simplex ProcartaPlexTM (Affymetrix, USA). Results. There are four levels of seven biomarkers of neoangiogenesis and inflammation method for multiplex analysis in patients with heart failure. A year after transplantation, the mean levels of biomarkers VEGF-A (p = 0.001), PDGF-BB (p = 0.018), MCP-1 (p = 0.003) was significantly decreased, and the others had a tendency to decrease relative to the level before transplantation. It was shown individual differences of levels of VEGF-A, VEGF-D and PlGF before and after transplantation. There were found different dynamics of the concentrations of biomarkers and growth factors before and after heart transplantation in patients with cardiovascular complications and without them. Conclusion. Multiplex analysis allows to measure the concentration range of analyte biomarkers of neoangiogenesis, inflammation in one sample of blood serum of patients with severe heart failure and after transplantation. There are marked individual differences in the concentration of biomarkers in different clinical situations that may have clinical significance in the conduct and supervision of recipients after transplantation.

Background. Quality of life (QoL) is an important criterion for the treatment effi cacy that provides an important data regarding patient’s personal estimation of social adaptation and ability to perform daily duties.Methods. The study was aimed to evaluate QoL in cardiac transplant recipients. We have enrolled 42 stage D heart failure patients aged 29–61 (mean 39,23 ± 12,31 y/o), 38 males and 4 females, survived cardiac transplant surgery between Jan 2008 and Jan 2013. QoL was evaluated using the SF-36 survey prior to the heart surgery and during the follow-up period up to the 5 years.Results. Pre-operative assessment revealed low QoL indices of physical activity as well as general health status. Follow-up showed dramatic improvement in all QoL measures during 1 year after the surgery which was consistent through the whole observation period. There was an increase in physical functioning index by 2,8 times (p < 0,01), physical status dependent role functioning by 14 times (р

Aim of the study is to show the pathogenetic importance of myocardial revascularization and to estimate quantitatively effi ciency of the treatment of cardiac allograft vasculopathy after heart transplantation.Materials and methods. 30 percutaneous coronary interventions (PCI) were performed to recipients of heart transplant (8 men and 7 women, aged from 18 to 56 years), who were diagnosed with cardiac allograft vasculopathy by coronary angiography within the time period from 1,5 to 12 years after heart transplantation. Before revascularization and one week after tolerances to physical activity, volume characteristics of the left ventricle were defi ned and diastolic function of heart was estimated. Average term of observation after stenting was 35,5 ± 5,5 months.Results. Tolerance to physical activity (from 76,6 ± 8,5 to 116,9 ± 9,6 W), its duration (from 5,4 ± 2,2 to 8,5 ± 4,1 min) and rate pressure product – RPP (from 198 ± 15 to 247 ± 24 P < 0,05) increased. There was a restoration of diastolic function (Ve/Va from 0,57 ± 0,18 to 1,15 ± 0,2 P < 0,05). Signifi cant distinction in time frames of vasculopathy development, frequency and reasons of repeated interventions depending on age of patients is revealed. In the group of patients younger than 30 years of age (7 patients), the time interval between heart transplantation and vasculopathy development is twice shorter, than in more senior patient group, over 45 years old (8 patients). Young patients showed the expressed tendency to develop stent restenosis (20 coronary interventions).Conclusion. Dynamics in functional condition of the left ventricle as a result of revascularization confi rms the leading role of miocardial ischemia in pathogenesis of transplant insuffi ciency due to vasculopathy. The signifi cant factor infl uencing upon long-term result of coronary intervention is the age of the patient.

The analysis of clinical outcomes of cardiac transplantation is presented. The main directions of research on the development and implementation of methods for early diagnosis of adverse events and treatment of patients with heart transplant in V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation are given. Among the non-invasive methods of forecasting, assessment of the risk of cardiovascular complications in heart recipients being developed are: analysis of laboratory biomarkers involved in the formation of relationship of the graft and the recipient; ultrasound diagnosis of functional and structural remodeling of peripheral arteries. The issues of improving drug therapy are discussed. The importance of multidisciplinary approach, continuity in management of the patients with heart transplant is emphasized.

Neoangiogenesis in coronary heart disease is a protective reaction aimed to improve ischemic myocardial perfusion, by increasing the number and size of arterial collaterals. Placental growth factor (PlGF) is one of the key peptides regulating angiogenic processes in atherosclerosis. In particular, a number of investigators have shown that injection of recombinant PlGF into the system or regional blood flow can stimulate neoangiogenesis. On the other hand, there is evidence confirming the involvement of PlGF in the progression of atherosclerosis and in the development of acute coronary syndrome. In this connection, the problem of investigating the efficiency and safety of possible use of PlGF preparations, as well as its place in the diagnosis of coronary heart disease and acute coronary syndrome remains urgent

Objective: to study the diagnostic value of placental growth factor (PlGF) in patients with coronary heart disease (CHD). Subjects and methods. 151 patients (75 men and 76 women; mean age 58.9 ± 12.3 years), including 66 patients with exercise-induced stable angina, 32 with unstable angina, 32 with myocardial infarction, and 21 with no clinical signs of CHD), were followed up. Blood PlGF levels were measured in all the examinees; C-reactive protein (CRP) concentrations were also determined using a high-sensitivity method in the patients with CHD.Results. In the patients with acute coronary syndrome (ACS), the levels of PlGF were significantly higher than in those with exercise-induced stable angina and in healthy individuals (17.3 ± 11.4 versus 11.2 ± 7.3 and 8.8 ± 6.7 pg/ml; p < 0.001). Estimation of the diagnostic value of the determination of PlGF levels in the diagnosis of ACS in troponin-negative examinees revealed that the area under the ROC curve (AUC) was 0.76. The quality of a diagnostic model using CRP was inferior to that with PlGF (n = 45; AUC for PlGF = 0.79; that for CRP = 0.65).Conclusion. The elevated level of PlGF may be considered as a diagnostic marker for ACS, including in the absence of the higher levels of cardiac troponins.

Aim. The aim of this study was to define the role of preformed anti-HLA antibodies (anti-HLA) in antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) after heart transplantation. Materials and Methods. 140 heart transplant recipients were followed after heart transplantation performed for 106 dilated and 34 – ischemic cardiomyopathy. Anti-HLA was determined before transplantation by ELISA. Results. Recipients were divided into 2 groups: anti-HLA positive (n = 45, 32,1%) and anti-HLA negative (n = 95, 67,9%). The incidence of AMR in anti-HLA positive group was 12 (26,67%) and 11 (11,58%) in anti-HLA negative group. Risk of AMR was significantly higher in anti-HLA positive recipients (RR 2,3: 95% CI 1,02–4,81, р = 0,03). During first three years after transplantation CAV was diagnosed in 9 (20%) of anti-HLA positive recipients and in 7 (6,8%) of patients without anti-HLA. (RR 2,7: 95% CI 1,08–6,82, р = 0,03). Survival in freedom from CAV in anti-HLA negative recipients was much higher than in anti-HLA positive recipients (0,89 ± 0,07, 0,72 ± 0,06, resp. (p = 0,02)).Conclusions. The presence of preformed anti-HLA antibodies in candidates for heart transplantation increase the risk of AMR and CAV post transplantation in 2,3 and 2,7 times, respectively.

The associations between adiponectin levels and atherosclerotic remodelling of carotid arteries were investigated in 50 patients with coronary heart disease. Among patients with increased adiponectin levels, carotid atherosclerosis was less severe (significantly lower mean values of total plaque volume), while arterial wall elasticity was higher (lower mean values of arterial stiffness, Icompl), compared to individuals with lower adiponectin concentrations.

Aim. To measure the blood levels of pregnancy-associated plasma protein A (PAPP-A) and inflammatory markers in patients with various forms of coronary heart disease (CHD); to evaluate their diagnostic and prognostic role. Material and methods. The study included 75 patients with unstable angina (UA), acute myocardial infarction (AIM), and stable angina. The concentrations of PAPP-A, vascular adhesion molecule (sVCAM-1) and interleukin-6 (IL-6) were measured by immuno-enzyme method; the levels of C-reactive protein (CRP) and fibrinogen were measured by latex-enhanced micro-plate immuno-turbidimetry method. The follow-up period lasted for two years. Results. A significant elevation of PAPP-A, CRP, IL-6, and sVCAM1 levels was observed in UA and AMI patients. The level of PAPP-A was significantly higher in UA participants than in those with AMI, and demonstrated the highest sensitivity and specificity in UA diagnostics. Conclusion. PAPP-A could be used as a marker of acute coronary syndrome. Its elevated levels (>10mIU/l) predict adverse outcomes in CHD patients.